Cellular BioMechanics & BioMaterials
We explore the interaction between cells, their surrounding matrix, and biomaterials for the development of new muskuloskeletal treatment strategies. We design micro-environments that provide specific mechanical, geometrical, and biochemical signals to support and control endogenous healing cascades.
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Cell organisation and extracellular matrix formation in porous biomaterials
Biomaterials are used clinically to support tissue healing. However, the way tissue forms inside biomaterial pores is not fully understood. The process is often described as a layer-by-layer growth process where cells proliferate and fill the pore from the biomaterial wall to the pore center. However, traction forces generated by the cells strongly influence cell and extracellular matrix (ECM) organization, especially at early stages of tissue formation. We use macroporous collagen biomaterials and simplified 3D structures reproducing the biomaterial's pore architecture to investigate the role of cell forces and tissue contraction on extracellular matrix patterning. Our aim is to understand how a biomaterial's pore architecture can be used to achieve ECM patterns that structurally guide and thereby support tissue regeneration, e.g. in bone or cartilage defects.
Are mechanical or structural properties of the extracellular matrix altered by growth factors?
In contrast to an advanced understanding how Bone Morphogenetic Proteins (BMPs) influence cell behaviour, little is known about their effect on extracellular matrix formation in early stages of tissue regeneration. Using macroporous biomaterials as 3D environments, we investigate the process how primary cells build extracellular matrix in the presence or absence of BMP2. We are specifically interested in BMP2-induced alterations of biochemical and mechanical matrix properties. With this, we aim at a better understanding of alternative ways how BMPs influence bone tissue regeneration next to the chemo-attraction and differentiation of stem cells.
The role of mechanical strain of extracellular matrix fibers in directing the healing process
Cells are actively organizing their extracellular matrix (ECM). This active organization of ECM fibers suggest the important role of mechanical forces generated by the contractile cytoskeleton, which is transferred to the ECM through focal adhesion complexes. Among the ECM components, fibronectin and collagen play a very important role in development and healing process, which according to the previous research is highly mechano-regulated. We aim to gain a better insight into the mechanism of force transmission from the cells to ECM and the long range signals resulting in growth and remodeling in the healing process. Therefore, it is necessary to be able to probe the interaction between fibronectin and collagen and the strain dependency of their assembly and organization in regeneration. By seeding macroporous collagen scaffolds and producing 3D micro tissues that mimic the healing process in soft tissues and early stage of bone regeneration, we study the mechanism of load transfer from Fibronectin to collagen and the influence of tissue tension on cell function and ECM growth, using Fluorescent Resonance Energy Transfer (FRET).